Pakatikati mwa chaka cha 2017, Merck analengeza zotsatira zabwino ndi kuyesedwa kwake, zotsatira zofunikira kwambiri ndi kufufuza mankhwala, anacetrapib. Anacetrapib yakonzedwa kuti ikule HDL cholesterol ("zabwino" cholesterol). Merck anamasulidwa kuti, pamene anawonjezeredwa ku mankhwala a statin , anacetrapib inachepetsa kwambiri zizindikiro za zochitika za mtima kwa odwala omwe anali pachiopsezo cha matenda a mtima .
Chilengezocho chinadabwitsa kwambiri kwa akatswiri a mtima kwambiri.
Bwanji Chodabwitsa?
Anacetrapib ndi cholesterol ester kuteteza mapuloteni (CETP) inhibitor, kalasi ya mankhwala omwe cholinga chake chikuwonjezera kwambiri magazi a HDL cholesterol. Chifukwa chakuti mafuta ambiri a HDL apezeka ndi matenda ochepetsa mtima, akatswiri ambiri amakhulupirira kuti mankhwala osokoneza bongo omwe amaletsa CETP angakhale opindulitsa kwambiri kwa anthu omwe ali ndi vuto lalikulu la mtima.
Choncho, kuyambira m'ma 1990s makampani osiyanasiyana osokoneza bongo agwiritsira ntchito mabiliyoni ambiri a madola akuyambitsa ndikuyesera CETP zingapo. Akatswiri ofufuza mtima ndi ochita malonda anali ofanana poganiza kuti pang'ono mwa CETP inhibitors adzakhala blockbusters.
Izo sizinayambe mwanjira imeneyo. Ndipotu, kwa zaka zambiri chisanachitike chidziwitso cha 2017, Merc inhibitors yakhala ngati imodzi mwa "mtengo" wamtengo wapatali mu mbiri ya mankhwala.
Ngakhale Merck atayambanso kulengeza za kupambana ndi anacetrapib, akatswiri ambiri amakayikira kuti CETP inhibitors onse, kapena anacetrapib makamaka, adzakhala ndi zotsatira zabwino pamoyo wa anthu, kapena phindu la kampani iliyonse ya mankhwala.
Mbiri Yachidule ya CETP Inhibitors
Kuletsa mavitamini a CETP kunakhala kovuta kwa anthu opanga mankhwala m'zaka za m'ma 1990, pamene adaphunzira kuti makoswe omwe alibe CETP anali ndi mazinga a HDL ndi kukana matenda a atherosclerosis .
Posakhalitsa pambuyo pake (atachita kafukufuku adafunafuna iwo), anthu ambiri adadziŵikanso omwe anasinthika m'thupi lawo la CETP lomwe linagwirizanitsidwa ndi miyeso ya HDL komanso chiopsezo chochepa cha matenda a umphawi (CAD) .
Cholingacho chinali chodziwikiratu: Kungogwiritsa ntchito mankhwala omwe amalepheretsa CETP, ndipo udzakweza miyeso ya HDL ndipo potero umachepetsa matenda a mtima. Chifukwa choyesetsa mwakhama komanso ndalama zambiri, makampani ambiri osokoneza bongo anayambitsa mapulogalamu akuluakulu kuti achite zimenezo. Ndipo pofika zaka za m'ma 2000s, kuyesedwa kwachipatala ndi CETP zowonjezera zowonjezera zinayambika, kukondwera kwambiri komanso kuwerengera kwa nkhuku zisanayambe.
Kotero kudabwitsidwa kunali kwenikweni pamene, kwa zaka khumi, zotsatira za mayesero a kachipatala ndi CETP inhibitors anali (kunena pang'ono) akukhumudwitsa.
Poyamba mankhwala osokoneza bongo anali opcetrapib (Pfizer), mu 2006. Mu mayesero a ILLUMINATE, anthu omwe anali pachiopsezo chotere anadzidzidzidwa kuti alandire matendawa (kuphatikizapo statin). CETP inhibitor ikuwoneka kuti ikuchita zomwe aliyense akufuna kuti achite: Anthu omwe amalandira matendawa amatha kuwonjezeka ndi 72 peresenti ya HDL, ndipo 24 peresenti yachepetsa LDL cholesterol-kotero kuchepa kwakukulu kwa zochitika za mtima zinali kuyembekezera.
Komabe, zosiyana zinachitika. Pamapeto pa phunzirolo, anthu ambiri anawonjezeka pafupipafupi pa 25% pa zochitika za mtima, ndipo anthu oposa 58 peresenti amafa. Pfizer mwamsanga anasiya torcetrapib.
Akatswiri anadabwa kwambiri chifukwa chodabwa kwambiri. Chodabwitsacho chinasintha kuchoka pa zaka zotsatirazi, monga zina zomwe CETP inhibitors zikukula zikulephera kulepheretsa zotsatira, ngakhale kuwonjezeka kwakukulu kwambiri mu HDL cholesterol.
Mu 2012, Hoffman-La Roche anasiya chitukuko cha CETP inhibitor, dalcetrapib, pamene kafukufuku wam'mbuyo wa mayesero awo akuluakulu sanawonetsere chithandizo chamankhwala.
Ndipo mu 2015 Eli Lilly analepheretsa chitukuko chawo, chifukwa chomwecho.
Pofika chaka cha 2015, pafupifupi anthu onse ankakhulupirira kuti kuyendetsa CETP inhibitors kunasanduka khungu. Ndipotu, Merck anaganiza kuti amasiya kuyesedwa kwawo ndi anacetrapib panthawiyo, komabe anasankha kupitiriza.
Panthawi imene Merck anapanga chidziwitso cha June, 2017, chinali chowoneka bwino cha CETP inhibitor, osati cholephera, chomwe chinadabwitsa.
Njira Yonse, Palibe Amene Ayenera Kudabwa
Ngati tiyang'anitsitsa zomwe zimadziwika ndi HDL lipoproteins ndi CETP, zotsatira "zozizwitsa" zomwe zikuwonetsedwa ndi zosiyanasiyana CETP zivomezi sizingakhale zodabwitsa kwambiri.
Zikuoneka kuti zochita za puloteni ya CETP zimakhala zovuta kwambiri, ndipo zimakhala ndi zotsatira zosiyanasiyana pa khungu la kolera la HDL, komanso LDL cholesterol, komanso pazinthu zina zamadzimadzi. Chifukwa cha zovutazi, sizingatheke kutsogolo kutsogolo kwa momwe kuchepa kwa puloteni wa CETP kudzakhala ndi zotsatira za chipatala. Mabuku ofufuzira amapereka umboni wochuluka wakuti CETP chiletso chingapangitse zinthu kukhala zovuta panthawi zina.
Mwachitsanzo, pamene (monga taonera) anthu ena omwe ali ndi chiwerengero cha kuchepa kwa chibadwa cha CETP ali ndi miyeso ya HDL komanso kuchepa kwa matenda a mtima, ena omwe ali ndi mitundu yosiyanasiyana ya kuchepa kwa chikhalidwe cha CETP ali ndi miyeso ya HDL koma kuopsa kwa matenda a mtima. Zikuwoneka kuti mavitamini a CETP nthawi zina amalimbikitsa, ndipo nthawi zina amateteza ku, kuthamanga kwa matenda a atherosclerosis, malingana ndi momwe thupi limagwirira ntchito, pamtundu wawo wamagetsi, ndipo mwinamwake pazinthu zina.
Kuti tifotokoze mfundoyi, ochita kafukufuku akuwoneka kuti apeza chigawo cha anthu ochokera ku mayesero a ILLUMINATE omwe anali ndi ma genetic, omwe torcetrapib inachepetsera mavuto a mtima (ngakhale kuti zotsatirazi zimavulaza kwambiri anthu ambiri). Mwina kugwiritsa ntchito CETP zowonongeka kumafuna kusankha mosamala odwala, pogwiritsira ntchito maumwini ndi / kapena zamatsenga.
Mfundo ndi yakuti, kupambana kapena kulephera kwa CETP kutetezedwa ndi kovuta komanso kosiyanasiyana, ndipo aliyense amene amadzinenera kuti "wadabwa" ndi zotsatira zamagulu ndi mankhwalawa amalepheretsa kumvetsa momwe vutoli likuvutikira.
Kodi Anacetrapib Adzasintha Kwambiri?
Mu yesero la REVEAL, anthu opitirira 30,000 omwe ali ndi atherosclerotic vascular disease anali randomized kulandira mwina anacetrapib kuphatikizapo mkulu-dose atorvastatin kapena atoravstatin yekha. Pambuyo pa zaka zinayi, kunachepetsa 9% pamtima mwa anthu omwe alandira anacetrapib. Zotsatira zomwe zimayesedwa mu REVEAL yophunzira zinali zambiri za imfa kuchokera ku CAD, matenda a mtima , ndi chofunikira cha mitsempha yamakono revascularization (ndiko, opaleshoni ndi / kapena stent ). Komabe, panalibe kuchepa kwa chiwerengero cha imfa, komabe.
Mndandanda wofalitsa, Merck anasonyeza kuti iwo "adzaganizira ngati apereke" kuti avomereze mankhwala ndi FDA. Kuwoneka kotereku si zachilendo kwa kampani yofalitsa nkhani yofalitsa mankhwala poyesa kuyesa kwachipatala bwino. N'kutheka kuti ndikuzindikira kuti kukula kwa anacetrapib kumawonekera pang'ono, poyerekeza ndi zoopsa zomwe sizikudziwika kuchokera kwa mankhwala a nthawi yayitali ndi mankhwalawa.
Anacetrapib imasungidwa nthawi yayitali m'ma maselo, ndipo imakhalabe m'thupi kwa nthawi yaitali. Izi zikhoza kukhala zodetsa nkhaŵa ngati, nkuti, zosavuta koma zoopsa zowononga potsiriza zimapezeka. Ichi ndi chimodzi chimene kampaniyo iyenera "kuganizira" pamene ikuganiza kuti ipite patsogolo.
Kotero zikuwoneka kuti Merck amayembekeza zinthu zazikulu kuchokera ku mankhwalawa, ndipo zikuwoneka kuti sizingatheke kuti anacetrapib idzakhala yotchedwa blockbuster CETP inhibitor yomwe aliyense ankayembekezera.
Pakali pano zikuwoneka kuti anacetrapib ikhoza kukhala, ngati paliponse, katswiri wothandizira kuika mtima kwa mtima.
Mawu Ochokera
Merck adalengeza kuti zotsatira zake zidzakhala bwino mu chipatala chawo ndi CETP inhibitor anacetrapib, pamene akulimbikitsa, ayenera kuyang'anitsitsa pa nthawi ino.
Chifukwa cha mbiri yakale ya ma ChibP inhibitors, zina mwazidziwitso za mankhwalawa, komanso kuti Merck mwiniyo sawoneka molakwika pa mankhwalawa, sitiyenera kusangalala kwambiri panthawi ino ya anacetrapib monga njira yatsopano yochepetsera mtima .
> Zotsatira:
> Kosmas CE, DeJesus E, Rosario D, et al. CETP Kuletsa: Zolephera Zakale ndi Chiyembekezo Cham'tsogolo. Clinical Medicine Zosintha: Maphunziro a Cardiology 2016: 10 37-42 do: 10.4137 / CMC.S32667.
> Gulu la HPS3-TIMI55-REVEAL Ogwirizanitsa. Zotsatira za Anacetrapib mu Odwala ndi Atherosclerotic Matenda Ochepetsa Matenda (ZOCHITIKA). N Engl J Med 2017; do: 10.1056 / HEJMoa170664.